Recurrent aphthous ulceration (RAU) is a common but troublesome chronic disease. The cause is unknown, although immunological factors have been implicated. Circulating antibody to fetal oral mucosa has been found, suggesting an autoimmune antibody-mediated mechanism. However, this antibody does not appear to be directly cytotoxic. There is also evidence suggesting a role for lymphocytotoxicity in the pathogenesis of the disease. However, recent studies suggest a mild impairment of cellular immunity. It is suggested that the pathogenesis of RAU involves a complex interaction between antibody, lymphocytes and the target tissue. Current concepts of immunological homeostasis postulate a balance between effector and regulatory mechanisms. Aspects of RAU which may reflect both of these mechanisms will be studied. Antibody-dependent cellular cytotoxicity (ADCC) has been implicated in the pathogenesis of several autoimmune diseases. Specific ADCC mechanisms will be evaluated in patients with RAU and controls. Several laboratories have recently shown that subtle defects in T-cell function can be demonstrated by stimulation of peripheral blood lymphocytes using suboptimal doses of phytohemagglutunin (PHA). A PHA dose-response assay with RAU patients' lymphocytes will be used to measure the presence and extent of this T-cell dysfunction.